Structure of human Stabilin-1 Interacting Chitinase-Like Protein (SI-CLP) reveals a saccharide-binding cleft with lower sugar-binding selectivity

Academic Article


  • Human secreted protein stabilin-1 interacting chitinaselike protein (SI-CLP) has been identified as a novel member of Glyco-18 domain-containing proteins that is involved in host defense and inflammatory reactions. Efficient secretion of SI-CLP is mediated by its interaction with the endocytic/ sorting receptor stabilin-1. SI-CLP is expressed abundantly in macrophages and neutrophils and is up-regulated by Th2 cytokine IL-4 and glucocorticoid, which suggest that SI-CLP could be a marker for adverse effects of glucocorticoid therapy. To gain insight into the biological function of SI-CLP, we determined the crystal structure of SI-CLP at 2.7 Å resolution by x-ray crystallography and found that it featured a typical triose-phosphate isomerase barrel fold with a putative saccharide-binding cleft. Comparison with other chitinase-like proteins showed the cleft to be atypically wide and open. The saccharide-binding capacity of SI-CLP was investigated, and its ligand-binding specificity was found to relate to the length of the oligosaccharides, with preference for chitotetraose. Further investigations reveal that SI-CLP could bind LPS in vitro and neutralize its endotoxin effect on macrophages. Our results demonstrate the saccharide-binding property of SICLP by structure and in vitro biochemical analyses and suggest the possible roles of SI-CLP in pathogen sensing and endotoxin neutralization. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
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    Digital Object Identifier (doi)

    Author List

  • Meng G; Zhao Y; Bai X; Liu Y; Green TJ; Luo M; Zheng X
  • Start Page

  • 39898
  • End Page

  • 39904
  • Volume

  • 285
  • Issue

  • 51